The overall objective of this study is to determine the role of the tumor-associated collagen matrix in the development of breast tumors. Various areas of dimethyl benz (a) anthracene (DMBA)-induced rat breast tumors were analyzed for collagen synthesis. Approximately 90% of the connective tissue samples adjacent to the tumors and 60% of the actual tumor had a greater absolute rate of collagen synthesis than did normal breast connective tissue distant from the tumor. No correlations could be made between the rate of tumor development, tumor size and the rate of collagen synthesis in or surrounding the tumor. Histologically, the tumor contained a heterogenous mixture of neoplastic cells, connective tissue cells and inflammatory cells, whereas the tumor-associated connective tissue predominately contained fibroblasts and Mallory trichrome staining material characteristic of collagen. These results suggest that there is a host-mediated, fibrotic response in tissue adjacent to the tumor. The effect of collagen cross-linking inhibition by the lathrogen beta-aminopropiontrile will be studied to determine if in the absence of normal insoluble collagen there are increased tumor numbers and tumor size. In contrast, agents which enhance the fibrotic response will be used to determine if increased fibrosis around the tumor causes decreased tumor numbers and tumor size. In addition, the effect of insulin and prolactin on collagen metabolism and clinical development or regression of DMBA-induced rat mammary tumors will be studied in these hormone-dependent tumors. BIBLIOGRAPHIC REFERENCES: Diegelmann, R.F., Rothkopf, L.C., and Cohen, I.K.: Measurement of collagen synthesis during wound healing. J. Surg. Res. 19:239, 1975. Cohen, I.K., Bryant, C.P., and Diegelmann, R.F.: Alpha globulin collagenase inhibitors in keloid and hypertrophic scar. Surgical Forum XXVI:61, 1975.